Genetically engineered mouse models of Parkinson's disease.
Genetically engineered mouse models of Parkinson's disease.
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DOI：
10.1016/j.brainresbull.2011.07.019
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发表时间：
2012-05-01
影响因子：
3.8
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Crabtree DM;Zhang J
帕金森氏病(PD)是最常见的神经退行性运动障碍，影响60岁以上人口的1%以上。帕金森病最常见的特征是静止性震颤，尽管有许多全身神经系统的影响，如大小便失禁和睡眠障碍。帕金森病的组织病理学特征是存在路易小体(Lb)，即主要由α-突触核蛋白组成的蛋白质包涵体。到目前为止，还没有有效的治疗方法来减缓或阻止疾病的进展。为了帮助了解疾病的发病机制和确定潜在的治疗靶点，已经开发了许多遗传小鼠模型。到目前为止，这些模型中最常见的是野生型和突变型α-突触核蛋白转基因小鼠，因为α-突触核蛋白是第一个被证明对帕金森病的发病和进展有直接影响的蛋白质。目前还有许多其他基因中断或突变的模型可用，这些模型是基于人类疾病中发现的遗传异常。此外，也有一些模型检查可能导致疾病发生或发展的基因，但目前尚未发现致病的PD突变。这些基因是黑质纹状体通路中维持神经元功能的重要信号通路的一部分。本文将对目前用于帕金森病研究的最常用的小鼠遗传模型进行综述。我们将研究这些模型如何扩大了我们对帕金森病发病机制和进展的理解，以及如何帮助确定这种疾病的潜在治疗靶点。
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, affecting more than 1% of the population over age 60. The most common feature of PD is a resting tremor, though there are many systemic neurological effects, such as incontinence and sleep disorders. PD is histopathologically identified by the presence of Lewy bodies (LB), proteinaceous inclusions constituted primarily by α-synuclein. To date, there is no effective treatment to slow or stop disease progression. To help understand disease pathogenesis and identify potential therapeutic targets, many genetic mouse models have been developed. By far the most common of these models are the wildtype and mutant α-synuclein transgenic mice, because α-synuclein was the first protein shown to have a direct effect on PD pathogenesis and progression. There are many other gene-disrupted or -mutated models currently available, which are based on genetic anomalies identified in the human disease. In addition, there are also models which examine genes that may contribute to disease onset or progression but currently have no identified causative PD mutations. These genes are part of signaling pathways important for maintaining neuronal function in the nigrostriatal pathway. This review will summarize the most commonly used of the genetic mouse models currently available for PD research. We will examine how these models have expanded our understanding of PD pathogenesis and progression, as well as aided in identification of potential therapeutic targets in this disorder.
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影响因子：
82.9
作者：
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通讯作者：
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影响因子：
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通讯作者：
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